Structure-based Virtual Screening Approaches in Kinase-directed Drug Discovery

Author(s): David Bajusz, Gyorgy G. Ferenczy, Gyorgy M. Keseru*.

Journal Name:Current Topics in Medicinal Chemistry

Volume 17 , Issue 20 , 2017

Graphical Abstract:


Abstract:

Protein kinases are one of the most targeted protein families in current drug discovery pipelines. They are implicated in many oncological, inflammatory, CNS-related and other clinical indications. Virtual screening is a computational technique with a diverse set of available tools that has been shown many times to provide novel starting points for kinase-directed drug discovery. This review starts with a concise overview of the function, structural features and inhibitory mechanisms of protein kinases. In addition to briefly reviewing the practical aspects of structure-based virtual screenings, we discuss several case studies to illustrate the state of the art in the virtual screening for type I, type II, allosteric (type III-V) and covalent (type VI) kinase inhibitors. With this review, we strive to provide a summary of the latest advances in the structure-based discovery of novel kinase inhibitors, as well as a practical tool to anyone who wishes to embark on such an endeavor.

Keywords: Drug discovery, Kinase, Structure-based virtual screening, Inhibitor, Docking, DFG motif, Activation segment, hinge, Covalent docking.

Rights & PermissionsPrintExport

Article Details

VOLUME: 17
ISSUE: 20
Year: 2017
Page: [2235 - 2259]
Pages: 25
DOI: 10.2174/1568026617666170224121313
Price: $58

Article Metrics

PDF: 24
HTML: 2
EPUB: 0
PRC: 0